The long term goal of the experiments proposed is to identify how neural control of reproduction is regulated. Specifically, what anatomical pathways control cellular and molecular actors that regulate the reproductive system. We will continue using a well defined teleost fish model system in which we manipulate the reproductive status of animals under controlled laboratory conditions mimicking natural events and measure the cellular and molecular consequences in identified neurons. We focus on gonadotropin-releasing hormone neurons (GnRH) in the hypothalamic-preoptic area using cellular and molecular probes and a newly developed GnRH transgenic animal. Environmental stimuli alone, depending on their valence, can cause GnRH containing neurons to enlarge or shrink ca. 8-fold in volume in this species. We have recently discovered that when animals are reproductively active, the dendritic arbors of GnRH neurons grow and the neurons appear to be coupled. This system allows realistic in vivo manipulation of the GnRH system providing an essential tool for discovering how external signals regulate the brain and its cellular and molecular processes. Since GnRH neurons are phylogenetically ancient and central to the control of reproduction in all vertebrates, these experiments will provide insight about the cellular and molecular mechanisms regulating reproduction across vertebrate phyla. We will address several key questions about the cellular and molecular changes responsible for controlling reproductive competence: 1) Do dendritic arbors of GnRH neurons enlarge, mediating interconnections in reproductively competent males and shrink, and disconnect in reproductively incompetent males? How are the synaptic connections different in number and kind between reproductively competent and incompetent males? 2) What genes are differentially expressed in GnRH neurons of reproductively competent males versus non-competent males? 3) What brain nuclei are active in the transition between reproductively competent and non- competent states and what are their anatomical connections to the GnRH neurons? 4) Are the GnRH neuronal firing patterns different between reproductively competent and non- competent males? What inputs regulate these firing patterns? PUBLIC HEALTH RELEVANCE This research is directed at understanding what neural signals control reproduction. Discovering how the brain controls reproduction will extend our knowledge of this critical physiological process. Since a healthy reproductive system is critically important for reproductive success, greater knowledge of how reproduction is regulated will contribute to better public health.